Radioprotective effects of black seed (Nigella sativa) oil against hemopoietic damage and immunosuppression in gamma-irradiated rats

Background and aim:?Sixty male Wistar rats, divided into 4 groups, 15 each, were designed as I-control rats, II-rats orally intubated with Nigella sativa oil (1?ml/kg b.wt./day) for 5 days/week, III-whole body gamma irradiated rats with the estimated LD50/30 (4 Gray) and IV-rats daily intubated with Nigella sativa oil then subjected to whole body gamma irradiation, to investigate the radioprotective potential of Nigella crude oil against hemopoietic adverse effects of gamma irradiation.

Results:?Irradiation resulted in significant reduction in hemolysin antibodies titers and delayed type hypersensitivity reaction of irradiated rats, in addition to significant leukopenia and significant decrease in plasma total protein and globulin concentrations and depletion of lymphoid follicles of spleen and thymus gland. Furthermore, there was a significant increase in malondialdehyde concentration with a significant decrease in plasma glutathione peroxidase, catalase and erythrocyte superoxide dismutase activities were recorded. Oral administration of Nigella sativa oil before irradiation considerably normalized all the above-mentioned criteria; and produced significant regeneration in spleen and thymus lymphoid follicles.

Conclusion:?Our results strongly recommend Nigella sativa oil as a promising natural radioprotective agent against immunosuppressive and oxidative effects of ionizing radiation.     

Oxidative DNA damage and cytogenetic effects in flight engineers exposed to cosmic radiation

This study set out to analyze biomarkers for genotoxic events, e.g., oxidative DNA damage, chromosomal damage and hprt mutations, among flight personnel, who are known to be occupationally exposed to ionizing radiation of cosmic origin. Twenty-three flight engineers were recruited while ground personnel served as a matched control group. Cumulative radiation doses during flight were calculated on the basis of subjects' flight records assuming an exposure rate of 6 μSv per hour of flight. Oxidative DNA damage in peripheral lymphocytes from flight engineers appeared significantly increased in comparison with controls and was associated with cumulative exposure to cosmic radiation. Frequencies of peripheral lymphocyte chromosome aberrations, micronuclei and hprt mutations appeared also to be increased in flight engineers, but not significantly. It was also observed that DNA damage was higher in flight engineers with a relatively shorter flight history in comparison with flight engineers with higher cumulative exposures to radiation, suggesting adaptation to DNA damage caused by ionizing radiation. DNA repair activities measured as unscheduled DNA synthesis were clearly increased in the higher-exposed subgroup of flight engineers, and appeared significantly correlated with cumulative radiation dose, as well as inversely with oxidative DNA damage. The implications for cancer risk assessment in relation to exposure to cosmic radiation are discussed. Environ. Mol. Mutagen. 32:121–129, 1998 © Wiley-Liss, Inc.     

DNA damage and repair capacity in workers exposed to low concentrations of benzene

DNA damage and cellular repair capacity were studied in 18 male fuel tanker drivers and 13 male filling‐station attendants exposed to low and very low concentrations of benzene, respectively, and compared to 20 males with no occupational exposure (controls). Exposure to airborne benzene was measured using passive personal samplers, and internal doses were assayed through the biomarkers t,t‐muconic acid, S‐phenylmercapturic acid and urinary benzene. DNA damage was evaluated using tail intensity (TI) determined by the comet assay in peripheral lymphocytes. Urinary 7‐hydro‐8‐oxo‐2’‐deoxyguanosine (8‐oxodG) was measured as a biomarker of oxidative damage. DNA repair kinetics were assessed using the comet assay in lymphocytes sampled 20 and 60 min post H₂O₂ exposure. Benzene exposure differed significantly between the drivers (median 246.3 µg/m³), attendants (median 13.8 µg/m³), and controls (median 4.1 µg/m³). There were no differences in TI and 8‐oxodG among the three groups, or between smokers and non‐smokers. DNA repair kinetics were similar among the drivers, attendants and controls, although the comet assay on H₂O₂‐damaged lymphocytes after 60 min revealed significantly lower levels of TI only in drivers. The DNA repair process in smokers was similar to that observed in drivers. In conclusion, this study found no relationship between low levels of benzene exposure and DNA damage, although there was evidence that exposure interferes with DNA repair kinetics. The biological impact of this finding on the onset of genotoxic effects in exposed workers has still to be ascertained. Environ. Mol. Mutagen. 57:151–158, 2016. © 2015 Wiley Periodicals, Inc.     

Ultrastructure of the pinealocytes in rats exposed to light and radiation

Changes in pinealocytes (PC) were analysed using quantitative electron microscopy in 240 adult male rats from first minutes up to 180 days after their continuous exposure to bright light (CLE) for 48 hours, X-ray irradiation (XRI) or their combination (CE). After CLE early changes of PC included the reduction of rough endoplasmic reticulum (RER), Golgi complex and synaptic ribbons. At 24 hours and 10 days PC secretory activity was increased, while their ultrastructural organization was normalized by 30-180 days. 10 days after XRI degenerative changes were detected in PC that included dilation, fragmentation and vacuolization of RER cisterns, mitochondrial swelling, appearance of large vacuoles and osmiophilic inclusions, increase in lysosome content. Volume density of mitochondria and RER was lower, while that of Golgi complex was higher than in control. PC ultrastructure was restored 30-180 days after XRI. Following CE, the changes in PC ultrastructural organization were more significant at all time interval studied than after the action of single factors. The results obtained indicate that CLE increased the extent of postradiation changes in PC ultrastructural organization during the early time intervals after XRI and at the peak of radiation sickness development.     

Effect of ubiquinone-10 on the blood system in rats exposed to radiation

The use of synthetic ubiquinone-10 (2 and 10 mg/kg) as a therapeutic food additive normalized the counts of erythrocytes, reticulocytes, and leukocytes and the content of hemoglobin in the blood and inhibited lipid peroxidation in erythrocytes in irradiated rats (3 Gy).     

Oxidative damage in substantia nigra and striatum of rats chronically exposed to ozone

The purpose of this work was to study if chronic low-dose ozone exposure could per se induce oxidative damage to neurons of striatum and substantia nigra. Thirty male Wistar rats were divided into three groups--Group 1: exposed to an air stream free of ozone; Group 2: exposed for 15 days to ozone; Group 3: exposed for 30 days to ozone. Ozone exposure was carried out daily for 4 h at a 0.25 ppm dose. Each group was then tested for (1) motor activity, (2) quantification of lipid peroxidation levels, (3) Klüver-Barrera staining, and (4) immunohistochemistry for tyrosine hydroxylase (TH), dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kD (DARPP-32), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD), to study neuronal alterations in striatum and substantia nigra. Results indicate that ozone exposure causes a significant decrease in motor activity. Ozone produced lipid peroxidation, morphological alterations, loss of fibers and cell death of the dopaminergic neurons. The DARPP-32, iNOS and SOD expression increased with repetitive ozone exposure. These alterations suggest that ozone causes oxidative stress which induces oxidative damage to substantia nigra and striatum of the rat.     

Assessment of genotoxic effects related to chronic low level exposure to ionizing radiation using biomarkers for DNA damage and repair

The first objective of our study was to analyse whether biomarkers for genotoxic effects (DNA breaks and alkali-labile sites and micronucleus and non-disjunction frequencies) could be fully validated for biomonitoring workers chronically exposed to ionizing radiation (IR). Blood samples of controls and individuals chronically exposed to IR were analysed. The interindividual variation was reduced when the comet data were adjusted for interexperimental variation, but remained statistically significant. No differences were found between groups, either for smoking or for exposure status. The second objective was to determine whether the Comet assay can be used to evaluate global repair phenotype as a susceptibility biomarker for IR-induced DNA damage in nuclear workers. A pilot study was performed and blood from workers exposed or not to radiation was submitted to a challenging dose of gamma-rays. The repair kinetics of each individual donor were analysed by Comet assay at different time points and compared with the frequencies of biomarkers of genotoxic effects. There was a statistically significant interaction between biomarkers assessing the same damage (micronucleus and Comet assays). Multivariate analysis showed that micronucleus frequencies were positively influenced by age and the percentage of residual tail length was negatively influenced by the interaction between smoking and exposure status. The general conclusions from our study are: (i) a positive correlation exists between mechanistically related biomarkers; (ii) multivariate regression analysis confirmed that the interaction between smoking and exposure to IR negatively and statistically significantly influenced residual tail length; (iii) use of the Comet assay for the estimation of global repair phenotype with respect to IR is recommended because it is simple, fast and differences in in vitro repair capacity can be detected.     

Normal human fibroblasts exposed to high- or low-dose ionizing radiation: differential effects on mitochondrial protein import and membrane potential

How oxidative metabolism modulates effects of ionizing radiation is incompletely understood. Because mitochondria participate in oxidative metabolism, we investigated the modulation of mitochondrial protein import and membrane potential (DeltaPsi) in irradiated cells. Our data show that effects at low dose cannot be predicted from effects at high dose. When density-inhibited normal human fibroblasts were exposed to a toxic dose of 4 Gy, protein import into mitochondria isolated from these cells was decreased. In contrast, protein import into mitochondria isolated from low-dose-irradiated (10 cGy) cells was enhanced, suggesting that mitochondria may play a crucial role in low-dose-induced adaptive responses. At high dose, import defects were not solely due to changes in mitochondrial DeltaPsi, and modulation of import was not tightly linked to the cellular capacity to repair radiation damage. Another striking observation is that in proliferating nonirradiated cells, mitochondrial protein import and DeltaPsi were regulated in a cell cycle-dependent manner, being lower in S phase than in G (1). Interestingly, when quiescent G (0)/G (1) phase cells exposed to high-dose radiation were stimulated to proliferate, events associated with S phase, but not G (1), significantly affected import. The strategy described here may serve as novel end points to study radiation-induced effects.     

The effects of whole body vibration and exercise on fibrinolysis in men

Whole body vibration (WBV) is a novel modality that has been demonstrated to enhance muscular and cardiovascular functions reported to increase fibrinolytic activity. The purpose of this study was to examine the fibrinolytic response to WBV and exercise in men. Twenty healthy males (23.8 ± 0.9 years, 25.6 ± 0.2 kg m⁻²) participated in the study. Each subject performed three trials in randomized order separated by 1 week: exercise (X), vibration (V) and vibration + exercise (VX). Exercise sessions consisted of 15 min of unloaded squatting at a rate of 20 per minute. Vibration sessions were conducted on a WBV platform vibrating for 15 min. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) were assessed at baseline and immediately after each condition. The increase in tPA activity was significantly greater in VX (0.87 ± 0.35 to 3.21 ± 1.06 IU ml⁻¹) compared to X (0.71 ± 0.36 to 2.4 ± 1.13 IU ml⁻¹) or V (0.83 ± 0.25 to 1.00 ± 0.37 IU ml⁻¹) conditions, and greater in the X condition compared to the V condition. PAI-1 activity decreased significantly more in the VX (6.54 ± 5.53 to 4.89 ± 4.13 IU ml⁻¹) and X (9.76 ± 8.19 to 7.48 ± 7.11 IU ml⁻¹) conditions compared to the V (5.68 ± 3.53 to 5.84 ± 3.52 IU ml⁻¹) condition. WBV does not augment fibrinolytic activity in healthy men. However, WBV combined with squatting exercise increases fibrinolytic activity more than exercise alone.     

Assessing liver proteins and enzymes of medical workers exposed to ionizing radiation (IR)

The cross-sectional study was conducted to examine hepatic function via liver enzymes/proteins assessments, along with the estimation of an inflammatory response from C-reactive protein (CRP)—which is a liver-synthesized protein. The liver function tests with aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin (BBN), and CRP test were conducted for radiation-exposed workers—REW (n = 32) and radiation-unexposed workers—RUW (n = 21). The annual average effective doses (AAED) were measured from thermoluminescent dosimeter. A t test and bivariate correlation analyses were applied. Only one worker had a high AST value (50 U/L), one worker had a negligible high ALT value (43 U/L) and only one worker had a negligible high bilirubin value (1.3 g/dL). There were normal levels of CRP (up to 6 mg/L) in all individuals. There existed a nonsignificant difference (p < 0.050) between the mean values of liver enzymes and proteins in all exposed and unexposed workers. Nonsignificant weak correlations are reported in liver enzymes/proteins parameters: AST, ALT, ALP, BBN, CRP with the AAED range (whole-body: 0.91–3.39 mSv) during 2011–2015. The normal values of liver enzymes/proteins’ (AST, ALT, ALP, BBN, CRP) values may ensure a good hepatic health of radiation-exposed medical workers with AAED range mentioned. We found that low ionizing radiation doses did not alter the liver function test parameters and did not affect the concentration of an inflammatory response protein, i.e., CRP.     

Sensitizing effect of Reverin (pyrrolidinomethyltetracycline) on the radiation damage of rat embryos as compared to its effect on other cell systems

The effect of Reverin (pyrrolidino-methyl-tetracycline) an inhibitor of protein synthesis on radiation damage (mainly in the head region) in 9-day-old rat embryos has been investigated and compared with its effects on other cell systems. An administration of 91.0 mg/kg body weight Reverin alone had a teratogenic effect. If Reverin was injected i.m. or i.p. 1 hour before irradiation the number of eye anomalies in 13-day-old fetuses was increased from 25.8% (irradiation only) to 58.8%. This enhanced effect was not due to an additive but to a synergistic mechanism. However Reverin failed to show synergistic effects on growth of Ehrlich carcinoma cells in ascites- and solid form as on chromosomal aberrations of normal chinese hamster cells, the death rate of irradiated chinese hamster cells was sensitized. It is proposed that tetracyclines act mainly on the immediate repair by blocking repair enzyme systems or by depression of energy metabolism. Differences in the reactions of other cell systems can be explained by a different biological relevance or vulnerability of repair systems.     

全身振动对中药轻粉(Hg2Cl2)在小鼠体内的药代动力学的影响

本文研究了小鼠单次轻粉灌胃给药后全身振动对小鼠体内血液、肝、肾、脑组织中含汞量分布的影响,发现50 Hz组的全身振动血液、肝、肾、脑组织吸收峰值均比对照组提前,20 Hz组的全身振动血液、肾、脑组织吸收峰值比对照组提前,且50 Hz组的血液、脑组织中吸收峰值显著高于20 Hz组;小鼠连续灌胃给药5天后进行测定,发现50 Hz振动组肝、肾、脑组织的含汞量显著低于对照组。结果表明：全身振动能加快小鼠对轻粉的吸收和消除,抑制汞在各组织中的蓄积。     

Opposite effects of gentle handling on body temperature and body weight in rats.

Opposite effects of gentle handling on body temperature and body weight in rats. PHhe aim of this study was to measure the body weight set point when rats are being handled gently and thus experience emotional rise in body temperature. Wistar male rats were used in this experiment, and each rat was its own control. Body weight set point was estimated from the rat's food hoarding behavior. The set point is the intersection of the regression line for hoarding with the X axis. During hoarding sessions the experimenter handled the rat and took its colonic temperature six to eight times, an action sufficient to arouse emotional fever. On alternate days the rats were not handled. Thus, body weight set point was obtained for each rat without handling and with handling. In sessions with handling, rats raised their body temperature, ate less, and defecated more than in control sessions. When handled, the body weight set point declined from 388 +/- 44 g to 366 +/- 47 g (p = 0.048, t = 2,39). The decline in the set point induced by gentle handling is believed to result from an elevation of the hypothalamic CRH.     

Protective effects of mate tea (Ilex paraguariensis) on H2O2-induced DNA damage and DNA repair in mice

Yerba mate (Ilex paraguariensis) is rich in several bioactive compounds that can act as free radical scavengers. Since oxidative DNA damage is involved in various pathological states such as cancer, the aim of this study was to evaluate the antioxidant activity of mate tea as well as the ability to influence DNA repair in male Swiss mice. Forty animals were randomly assigned to four groups. The animals received three different doses of mate tea aqueous extract, 0.5, 1.0 or 2.0 g/kg, for 60 days. After intervention, the liver, kidney and bladder cells were isolated and the DNA damage induced by H(2)O(2) was investigated by the comet assay. The DNA repair process was also investigated for its potential to protect the cells from damage by the same methodology. The data presented here show that mate tea is not genotoxic in liver, kidney and bladder cells. The regular ingestion of mate tea increased the resistance of DNA to H(2)O(2)-induced DNA strand breaks and improved the DNA repair after H(2)O(2) challenge in liver cells, irrespective of the dose ingested. These results suggest that mate tea could protect against DNA damage and enhance the DNA repair activity. Protection may be afforded by the antioxidant activity of the mate tea's bioactive compounds.     

The effects of extracorporeal whole body hyperthermia on the functional and phenotypic features of canine peripheral blood mononuclear cells (PBMC)

In this study the effect of transient 42.3 degrees C whole body hyperthermia (WBH) on the distribution of PBMC phenotypes and in vitro blastogenic responsiveness was determined in dogs. Hyperthermia (n = 6) was induced by heating venous blood during extracorporeal circulation (venous perfusion WBH); perfused non-heated dogs (n = 4) were used as controls. Both euthermic and hyperthermic perfusion produced transient lymphopenia which normalized in controls after perfusion but persisted in hyperthermic animals throughout the 8-day post-perfusion observation interval. The transient lymphopenia in control dogs was non-selective. In contrast, WBH-associated lymphopenia was selective, in that CD5+ T lymphocytes were more sensitive to hyperthermia than sIg+ B cells and, within the T cell compartment, suppressor (CD8+) cells were more sensitive to hyperthermic stress than helper (CD4+) lymphocytes. Functional analyses showed that WBH caused persistent suppression of PBMC blastogenesis in response to T cell phytomitogens. Increased plasma cortisol levels were correlated to peak lymphopenia and hyporesponsiveness to phytomitogens. Despite these alterations, high grade WBH was well tolerated and there was no evidence of opportunistic infection.     

Metabolic damage to the myocardium in normotensive and hypertensive rats (morphometric analysis)

Morphological changes of myocardium were demonstrated in normotensive Wistar rats and in rats with inherited stress-induced arterial hypertension 1, 7 and 30 days following adrenaline induced damage. In acute period contracture damage to cardiomyocytes was more pronounced in Wistar rats. Death of the fraction of cardiomyocytes is compensated by hypertrophy of the surviving cells already by d 7. In hypertensive rats' hypertrophied myocardium on d 1 microcirculatory bed is more impaired, while regenerative processes in cardiomyocytes are delayed and defective, which leads to dystrophy and degeneration by the end of the experiment. It is concluded that the course and prognosis of myocardial metabolic injury is determined by its initial state and potential compensatory resources.     

Orexins (hypocretins) contribute to fear and avoidance in rats exposed to a single episode of footshocks

Orexins (hypocretins) are peptides that have been shown to regulate behavioral arousal and wakefulness. Recent evidence indicates that orexin neurons are activated by stress and that orexins play a role in anxiety. The present paper describes a series of experiments that examined whether orexins are involved in the anxiety that resulted from exposing rats to an acute episode of footshocks (5 × 2 s of 1.5 mA shocks). We found that prepro-orexin (ppOX) mRNA was elevated in rats at 6 and 14 days after exposure to footshock and that ppOX mRNA levels were correlated with fear at 14 days post-shock. Systemic injections of the non-selective dual orexin receptor antagonist TCS-1102 (10 and 20 mg/kg, i.p.) were found to decrease fear and anxiety in rats 14 days after exposure to footshock. We also found that rats that exhibited a high level of immobility to a novel tone the day after the footshock episode (high responders, HR) showed significantly elevated levels of ppOX mRNA at 14 days post-shock compared to control rats. Furthermore, TCS-1102 (10 mg/kg, i.p.) was found to have anxiolytic effects that were specific for HR when tested in the elevated T-maze. This study provides evidence linking the orexin system to the anxiety produced by exposure of rats to a single episode of footshocks. It also provides preclinical evidence in support of the use of orexin antagonists for the treatment of anxiety in response to an acute episode of stress.